DOE Patents title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes

Abstract

The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.

Inventors:
; ; ; ;
Issue Date:
Research Org.:
California Institute of Technology (CalTech), Pasadena, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1177111
Patent Number(s):
8993262
Application Number:
14/185,861
Assignee:
California Institute of Technology (Pasadena, CA)
Patent Classifications (CPCs):
C - CHEMISTRY C12 - BIOCHEMISTRY C12N - MICROORGANISMS OR ENZYMES
C - CHEMISTRY C12 - BIOCHEMISTRY C12P - FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {
DOE Contract Number:  
FG02-06ER15762
Resource Type:
Patent
Resource Relation:
Patent File Date: 2014 Feb 20
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Coelho, Pedro S, Brustad, Eric M, Arnold, Frances H, Wang, Zhan, and Lewis, Jared C. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes. United States: N. p., 2015. Web.
Coelho, Pedro S, Brustad, Eric M, Arnold, Frances H, Wang, Zhan, & Lewis, Jared C. In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes. United States.
Coelho, Pedro S, Brustad, Eric M, Arnold, Frances H, Wang, Zhan, and Lewis, Jared C. Tue . "In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes". United States. https://www.osti.gov/servlets/purl/1177111.
@article{osti_1177111,
title = {In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes},
author = {Coelho, Pedro S and Brustad, Eric M and Arnold, Frances H and Wang, Zhan and Lewis, Jared C},
abstractNote = {The present invention provides methods for catalyzing the conversion of an olefin to any compound containing one or more cyclopropane functional groups using heme enzymes. In certain aspects, the present invention provides a method for producing a cyclopropanation product comprising providing an olefinic substrate, a diazo reagent, and a heme enzyme; and admixing the components in a reaction for a time sufficient to produce a cyclopropanation product. In other aspects, the present invention provides heme enzymes including variants and fragments thereof that are capable of carrying out in vivo and in vitro olefin cyclopropanation reactions. Expression vectors and host cells expressing the heme enzymes are also provided by the present invention.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Mar 31 00:00:00 EDT 2015},
month = {Tue Mar 31 00:00:00 EDT 2015}
}

Works referenced in this record:

Preparation of derivatives of cyclobutane and cyclobutene
patent, June 1976


Process for the preparation of an oxirane, azirdine or cyclopropane
patent, December 1997


Composition comprising methylphenidate and another drug
patent, September 2007


Regio- and enantioselective alkane hydroxylation with modified cytochrome P450
patent, January 2011


Cobalt-based catalysts for the cyclization of alkenes
patent-application, February 2006


Substituted sulfones and methods of use
patent-application, May 2006


Active Substance Combinations with Insecticidal Properties
patent-application, November 2007


Compounds and Pharmaceutical Compositions for the Treatment of Viral Infections
patent-application, September 2009


Method of Producing 6,6Dimethyl-3-Oxabicyclo[3.1.0] Hexan-2-One
patent-application, July 2010


Mutant Enzymes
patent-application, September 2010


Rubber Composition
patent-application, August 2011


Modified Drugs for Use in Liposomal Nanoparticles
patent-application, September 2012


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010


Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in Escherichia coli
journal, September 2010


Basic local alignment search tool
journal, October 1990


Basic local alignment search tool
journal, October 1990


The CCP4 suite programs for protein crystallography
journal, September 1994


C–H activation
journal, March 2007


Protein stability promotes evolvability
journal, March 2006


1-Aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants
journal, February 1987


Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways
journal, November 2004


Bringing chemistry to life
journal, August 2011


Biomimetic Chemistry: Biology as an Inspiration
journal, September 2008


Metal-Catalyzed Olefin Cyclopropanation with Ethyl Diazoacetate: Control of the Diastereoselectivity
journal, March 2009


C–H activation
journal, March 2007


Protein stability promotes evolvability
journal, March 2006


1-Aryl-2-(aminomethyl)cyclopropanecarboxylic acid derivatives. A new series of potential antidepressants
journal, February 1987


Catalytic Promiscuity in Biocatalysis: Using Old Enzymes to Form New Bonds and Follow New Pathways
journal, November 2004


Bringing chemistry to life
journal, August 2011


Biomimetic Chemistry: Biology as an Inspiration
journal, September 2008


A Self-Sufficient Peroxide-Driven Hydroxylation Biocatalyst
journal, July 2003


The role of Thr268 and Phe393 in cytochrome P450 BM3
journal, May 2006


A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo
journal, June 2013


Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes
journal, December 2012


Dirhodium Tetraprolinate-Catalyzed Asymmetric Cyclopropanations with High Turnover Numbers
journal, May 2003


Catalytic C–H functionalization by metal carbenoid and nitrenoid insertion
journal, January 2008


Catalytic Enantioselective C−H Activation by Means of Metal−Carbenoid-Induced C−H Insertion
journal, August 2003


Synthesis of cyclopropane containing natural products
journal, October 2001


Probing the molecular determinants of coenzyme selectivity in the P450 BM3 FAD/NADPH domain
journal, August 2009


Coot model-building tools for molecular graphics
journal, November 2004


Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins
journal, January 1991


Scaling and assessment of data quality
journal, December 2005


C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450
journal, February 2009


The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies
journal, March 2003


Pivotal Role of Water in the Mechanism of P450BM-3
journal, November 2001


General Method for Sequence-independent Site-directed Chimeragenesis
journal, July 2003


Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C-H Activation
journal, October 2012


Complex reactions catalyzed by cytochrome P450 enzymes
journal, March 2007


Integration, scaling, space-group assignment and post-refinement
journal, January 2010


Novel bioreduction system for the production of chiral alcohols
journal, October 2003


Stereoselective Cyclopropanation Reactions
journal, April 2003


Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3
journal, June 2009


Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases
journal, September 2009


Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates
journal, November 2010


Ruthenium-catalysed carbenoid cyclopropanation reactions with diazo compounds
journal, January 2004


Reaction of carbon tetrachloride with 5,10,15,20-tetraphenyl-porphinatoiron(II)[(TPP)Fe II ]: evidence for the formation of the carbene complex [(TPP)Fe II (CCl2)]
journal, January 1977


Engineering Cytochrome P450 BM3 for Terminal Alkane Hydroxylation
journal, April 2006


Iron-Catalyzed Cyclopropanation in 6 M KOH with in Situ Generation of Diazomethane
journal, March 2012


A Convenient Synthesis of Bifunctional Vicinal Cyclopropanes
journal, January 1978


Refinement of Macromolecular Structures by the Maximum-Likelihood Method
journal, May 1997


Construction of Catalase Deficient Escherichia coli Strains for the Production of Uricase
journal, January 1996


Asymmetric catalytic cyclopropanation reactions in water
journal, March 2008


Asymmetric catalytic cyclopropanation reactions in water
journal, March 2008


Phenylalanine 393 Exerts Thermodynamic Control over the Heme of Flavocytochrome P450 BM3
journal, November 2001


Structure-Guided Recombination Creates an Artificial Family of Cytochromes P450
journal, April 2006


Recent developments in asymmetric cyclopropanation
journal, July 2008


SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions
journal, November 2009


Semisynthesis of axial-ligand (position 80) mutants of cytochrome c
journal, January 1991


Development of a heme protein structure electrochemical function database
journal, December 2007


Highly cis -Selective Cyclopropanations with Ethyl Diazoacetate Using a Novel Rh(I) Catalyst with a Chelating N-Heterocyclic Iminocarbene Ligand
journal, February 2009


Cobalt-Catalyzed Intramolecular C−H Amination with Arylsulfonyl Azides
journal, November 2007


Catalyst structure and the enantioselective cyclopropanation of alkenes by copper complexes of biaryldiimines: the importance of ligand acceleration
journal, May 2001


Organometallic aspects of cytochrome P-450 metabolism
journal, March 1987


(.+-.)-(Z)-2-(Aminomethyl)-1-phenylcyclopropanecarboxamide Derivatives as a New Prototype of NMDA Receptor Antagonists
journal, July 1995


Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction
journal, July 2010


The Cytochrome P450 Engineering Database: integration of biochemical properties
journal, January 2009


MOLREP an Automated Program for Molecular Replacement
journal, December 1997


Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity
journal, September 2002


Dirhodium(II) Tetrakis[3(S)-phthalimido-2-piperidinonate]: A Novel Dirhodium(II) Carboxamidate Catalyst for Asymmetric Cyclopropanation
journal, January 1996


Biosynthesis and Metabolism of Cyclopropane Rings in Natural Compounds
journal, April 2003


Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin
journal, January 2012


Shape and stereoselective cyclopropanation of alkenes catalyzed by iron porphyrins.
journal, September 1995


Protein engineering as a tool for understanding electron transfer
journal, August 1993


Roles of the Proximal Hydrogen Bonding Network in Cytochrome P450 c am -Catalyzed Oxygenation
journal, December 2002


The role of Thr268 in oxygen activation of cytochrome P450BM-3
journal, November 1995


    Works referencing / citing this record:

    In vivo and in vitro olefin cyclopropanation catalyzed by heme enzymes
    patent, March 2015